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Also known as:GSD IXdGSD due to muscle phosphorylase kinase deficiencyGSD type 9D
Overview
A benign form of phosphorylase kinase deficiency caused by variants in PHKA1, characterized by exercise intolerance, myalgia, muscle cramps, myoglobinuria, and progressive muscle weakness.
GeneticsX-linked · PHKA1 (chr X)
Patient Orgs1 organizations · Association for Glycogen Storage Disease (UK) Ltd
Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.
Features include always present findings: Elevated creatine kinase (muscle enzyme) (elevated circulating creatine kinase concentration), Quadriceps muscle weakness, Reduced muscle phosphorylase kinase activity, and Distal amyotrophy and others. 17 total HPO annotations.
Glycogen storage disease type IX (GSD IX) is caused by PhK deficiency affecting primarily liver or muscle.
Liver PhK Deficiency
While liver PhK deficiency has been considered a mild condition, more severe involvement has been documented . The three subtypes, caused by pathogenic variants in three different genes (PHKA2, PHKB, and PHKG2), cannot be distinguished by their clinical features, which can vary significantly in severity. See also . Presentation. Typically, an affected child presents in the first years of life with hepatomegaly and growth restriction. Hyperketotic hypoglycemia, if present, is usually mild but can be severe and recurrent.
Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.
PHKA1 function has not been fully characterized.
Glycogen storage disease IXd is caused by mutations in the PHKA1 gene on chromosome X.
GeneReviews
Clinical Guidance
Pathogenic variants in PHKA1 result in muscle glycogenosis; pathogenic variants in PHKA2 and PHKG2 cause liver glycogenosis; pathogenic variants in PHKB and, rarely, PHKG2 cause liver and muscle glycogenosis (muscle signs are variably present). There is no consistent genotype-phenotype correlation for pathogenic variants in any of the four genes. Pathogenic variants in PHKG2 appear to result in more severe disease with an increased risk of liver fibrosis and cirrhosis, although persons with a milder course have been observed. Progressive liver disease has also been noted in individuals with pathogenic variants in PHKA2.
Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.
GeneReviews
Diagnostic Criteria
Phosphorylase kinase deficiency causing glycogen storage disease type IX (GSD IX) results from deficiency of the enzyme phosphorylase b kinase (PhK), an enzyme with a key regulatory role in the breakdown of glycogen. Deficiency of this enzyme, which is composed of four copies each of four subunits (, , , and ), results in considerable clinical variability . For the purposes of this review, phosphorylase kinase (PhK) deficiency has been divided into liver PhK deficiency and muscle PhK deficiency (see and ). Liver PhK deficiency is further divided into three subtypes based on the gene in which pathogenic variants occur (PHKA2, PHKB, and PHKG2) and inheritance pattern. It should be noted that pathogenic variants in PHKB and, rarely, PHKG2 result in PhK deficiency both in liver and muscle.
Table 3. Genetic Disorders to Consider in the Differential Diagnosis of Phosphorylase Kinase (PhK) Deficiency
PhK DeficiencyType
Disorder
MOI
Overlapping Features
Distinguishing Features
Gene(s)
Enzyme
Glycogen storage disease type VI
AR
Clinical features can be indistinguishable.
Genetic testing for PHKA1 is available. Testing is considered confirmatory for diagnosis.
Treatment
Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.
No approved treatments are currently available for glycogen storage disease IXd. The disease remains an area of unmet medical need.
GeneReviews
Management Guidelines
Evaluations Following Initial Diagnosis
To establish the extent of disease and needs of an individual diagnosed with liver PhK deficiency, the following evaluations are recommended if they have not already been completed:
Measurement of blood glucose concentration (normal 70 mg/dL) for two to three days:
Upon waking in the morning;
Prior to meals and nighttime supplementation with oral cornstarch; and
After activity
Measurement of blood ketone levels for two to three days:
Upon waking in the morning;
Prior to meals and nighttime supplementation with oral cornstarch; and
After activity.
Elevated blood ketones (beta-hydroxybutyrate 1.0 mmol/L) could be an indicator of suboptimal metabolic control and pending hypoglycemia.
Liver imaging, if not performed in the past year. The type of liver imaging (ultrasound, MRI, or CT) is determined by factors such as age and underlying liver status (e.g., liver cirrhosis).
Basic metabolic panel including liver enzymes (AST, ALT, and alkaline phosphatase)
Prothrombin time
Lipid panel (cholesterol and triglyceride concentrations)
Serum creatine kinase measurement (Some individuals with liver PhK deficiency have muscle involvement.)
Baseline echocardiogram (Baseline echocardiogram may be done as a precaution as interventricular septal hypertrophy was found in an individual with GSD IX caused by pathogenic variants in PHKB .)
Liver PhK deficiency. Affected Individuals should avoid the following:
Large amounts of simple sugars, as they will increase liver storage of glycogen and may result in rapid fluctuations in levels of blood glucose and insulin
Prolonged fasting
High-impact contact sports if significant (moderate to massive) hepatomegaly is present. The final decision is based on clinician judgment.
Drugs known to:
Cause hypoglycemia, such as insulin and insulin secretagogues (the sulfonylureas)
Mask symptoms of hypoglycemia, such as beta-blockers
Alcohol, as this may predispose to hypoglycemia
Glucagon, as glycogenolysis is defective
Augmentin®, as it can cause malabsorption and contains clavulanic acid, which is associated with idiopathic liver disease
Growth hormone therapy unless there is proven growth hormone deficiency, as it can promote ketosis and development of liver adenomas
Hypoglycemic events in adults with liver PhK deficiency are relatively uncommon; however, caution should be used with drugs causing potential hypoglycemia, particularly in persons with impaired liver function. Muscle PhK deficiency. Affected individuals should avoid the following:
GeneReviews
Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.
GeneReviews
Surveillance Guidelines
Liver PhK deficiency
Regular evaluation by a metabolic physician familiar with liver PhK deficiency to monitor medical issues and a metabolic nutritionist to give dietary recommendations and monitor cornstarch requirement
Regular monitoring of blood glucose concentration and ketones, as recommended by a metabolic physician and nutritionist. Blood glucose concentrations and ketones should also be measured during times of stress including illness, intense activity, rapid growth, puberty, and pregnancy; and at any time in which intake of food is reduced, or meal and/or cornstarch dose or scheduling is altered.
Note: It is possible that blood glucose concentrations may be normal when moderate to large ketosis in liver PhK deficiency results from increased fatty acid oxidation and upregulated gluconeogenesis. The role of ketone monitoring in this setting as a marker of metabolic control requires further systematic investigation.
Liver imaging. In children younger than age 18 years, liver ultrasound examination every 12 to 24 months. With increasing age, consideration of CT or MRI using intravenous contrast to evaluate for complications of liver disease such as liver adenomas and cirrhosis
Follow-up echocardiogram. No guidelines established; follow up approximately every two years or earlier if symptoms are present
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
Research Landscape
Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.
No clinical trials have been registered for glycogen storage disease IXd.
3 publications have been identified in PubMed for glycogen storage disease IXd. Research spans Case Report / Case Series (100%).
Recent Publications
Huynh T (2026). [PMID: 41660530](https://pubmed.ncbi.nlm.nih.gov/41660530/). *J Lipid Atheroscler*. [Case Report / Case Series]
Kawata K (2025). [PMID: 40923014](https://pubmed.ncbi.nlm.nih.gov/40923014/). *Surg Case Rep*. [Case Report / Case Series]
Koch RL (2025). [PMID: 41213961](https://pubmed.ncbi.nlm.nih.gov/41213961/). *NPJ Genom Med*. [Case Report / Case Series]
Data assembled from 8 of 12 sources · Last updated Nov 4, 2026, 2:22 PM UTC
Diseases are connected by shared genes, phenotypes, therapeutic targets, and MONDO disease hierarchy. The Rare badge reflects Kisho's rarity classification — scored from authoritative sources including OMIM, Orphanet, orphan drug designations, clinical trial activity, and published prevalence data.
→Should female family members consider carrier screening for PHKA1?
→Are there specialists or centers of excellence for this condition in my area?
→How can I connect with Association for Glycogen Storage Disease (UK) Ltd and other patient organizations for support?
In liver PhK deficiency: low liver glycogen phosphorylase activity on in vitro assay1
PYGL
—
—
Glycogen phosphorylase, liver form Glycogen storage disease type I(GSD I)
AR
Hepatomegaly; Hypoglycemia
In GSD I:; Severe fasting lactic acidosis; Hyperuricemia; Significant hyperlipidemia
—
—
—
Neutropenia In PhK deficiency: ketosis usually present
G6PC1,SLC37A4
Glucose-6-phosphatase
—
—
—
—
Glucose-6-phosphate exchanger SLC37A4 Glycogen storage disease type III(GSD III)
AR
Hepatomegaly; Hyperlipidemia
—
—
—
—
Hypoglycemia ketosis
In GSD III: hypoglycemia more severe muscle involvement w/ CK concentrations
AGL
—
—
—
—
Glycogen-debranching enzyme Glycogen storage disease type IV (GSD IV)
AR
Hepatomegaly; Liver cirrhosis; Liver dysfunction
In GSD IV:; Hypoglycemia ketosis not typically seen; No hypoglycemia in initial stages; Accumulation of an abnormal glycogen (amylopectin) in liver other tissues
GBE1
—
—
1,4-alpha-glucan-branching enzyme Fructose-1,6-bisphosphatase deficiency (Note: Other disorders of gluconeogenesis can also be considered.2)
In alpha-1-antitrypsin deficiency: lack of fasting hypoglycemia hyperlacticacidemia
SERPINA1
—
—
—
—
Alpha-1 antitrypsin Deoxyguanosine kinase deficiency (mitochondrial DNA depletion syndrome 3)
AR
Hepatomegaly; Hypoglycemia
In deoxyguanosine kinase deficiency:; Neurologic abnormalities; Lactic acidosis
DGUOK
—
—
Mitochondrial respiratory chain complexes (I, III, IV, V) Mitochondrial complex V (ATP synthase) deficiency (OMIM 604273)
AR
Hepatomegaly
In mitochondrial complex V deficiency:; Ataxia; Lactic acidosis
ATPAF2
—
—
ATP synthase Glycerol kinase deficiency (OMIM 307030)
XL
Hypoglycemia
In glycerol kinase deficiency:; Ketoacidosis; Extremely elevated glycerol
GK
—
—
Glycerol kinase Niemann-Pick disease type B4 (See Acid Sphingomyelinase Deficiency.)
AR
Growth restriction; Hepatomegaly; Hyperlipidemia
In Niemann-Pick disease type B:; Lack of fasting hypoglycemia; Significant splenomegaly; Storage cells characteristic of disease; Other features incl bone pulmonary involvement
(NASDAQ:BEAM) reported initial ... storage disease type Ia, according to a press release statement. The trial enrolled six patients who received a single intravenous infusion of BEAM-301 at doses of either 20 mg or 40 mg. Median follow-up was 7.6 months as of the August 17, 2026 data cutoff. The data was presented today at the European Society of Gene and Cell Therapy congress in ... (NASDAQ:BEAM) reported initial data from its Phase 1/2 clinical trial evaluating BEAM-301, an investigational treatment for glycogen storage disease type Ia, according to a press release statement. The trial enrolled six patients who received a single intravenous infusion of BEAM-301 at doses of either 20 mg or 40 mg. Median follow-up was 7.6 months as of the August 17, 2026 data cutoff. The data was presented today at the European Society of Gene and Cell Therapy congress in Hamburg, Germany. Beam reports early data on gene therapy for rare metabolic disease BEAM-301 is designed to correct the R83C mutation in the G6PC1 gene. This article was generated with the support of AI and reviewed by an editor.
Mereo BioPharma Group plc, a ... therapeutics for the treatment of oncology and rare diseases in the United Kingdom, the United States, and internationally. It develops Etigilimab (MPH-313), an antibody T-cell immunoreceptor with Ig and ITIM domains, which is in Phase 1b clinical trial for the treatment ... Mereo BioPharma Group plc, a biopharmaceutical company, develops and commercializes therapeutics for the treatment of oncology and rare diseases in the United Kingdom, the United States, and internationally. It develops Etigilimab (MPH-313), an antibody T-cell immunoreceptor with Ig and ITIM domains, which is in Phase 1b clinical trial for the treatment of tumors. Mereo BioPharma Group (NASDAQ:MREO – Get Free Report) and Ultragenyx Pharmaceutical (NASDAQ:RARE – Get Free Report) are both small-cap healthcare companies, but which is the superior investment? We will compare the two companies based on the strength of their earnings, profitability, dividends, analyst recommendations, valuation, institutional ownership and risk. The company is also developing Navicixizumab (OMP-305B83), which has completed Phase 1b clinical trials for the treatment of the late line ovarian cancer; Acumapimod (BCT-197), a p38 MAP kinase inhibitor that is in Phase II clinical trials to treat acute exacerbations of chronic obstructive pulmonary disease; and Leflutrozole (BGS-649), an oral aromatase inhibitor for the treatment of hypogonadotropic hypogonadism which is in Phase 2 trials. In addition, it develops rare disease product candidates, including Setrusumab (BPS-804), an antibody for the treatment of osteogenesis imperfecta; and Alvelestat (MPH-966), an oral small molecule that is in Phase II clinical trial to treat Alpha-1 anti-trypsin deficiency. The company's products candidatures include DTX401, an adeno-associated virus 8 (AAV8) gene therapy clinical candidate for the treatment of patients with glycogen storage disease type Ia; DTX301, an AAV8 gene therapy for the treatment of patients with ornithine transcarbamylase; UX143, a human monoclonal antibody for the treatment of osteogenesis imperfecta; GTX-102, an antisense oligonucleotide for the treatment of Angelman syndrome; UX111, an AAV9 gene therapy product candidate for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease; UX701, for the treatment of Wilson disease; and UX053 for the treatment of glycogen storage disease type III.
The FDA has approved Genglycos ... gene therapy, to reduce cornstarch dependence in patients eight and older with GSDIa, the first approved treatment to target the disease's underlying genetic cause. ... The FDA has granted accelerated approval to pariglasgene brecaparvovec-opnr (Genglycos) for adults and pediatric patients eight years of age and older with glycogen storage disease type Ia (GSDIa), a rare inherited disorder caused by ... The FDA has approved Genglycos (pariglasgene brecaparvovec-opnr), a one-time AAV8 gene therapy, to reduce cornstarch dependence in patients eight and older with GSDIa, the first approved treatment to target the disease's underlying genetic cause. ... The FDA has granted accelerated approval to pariglasgene brecaparvovec-opnr (Genglycos) for adults and pediatric patients eight years of age and older with glycogen storage disease type Ia (GSDIa), a rare inherited disorder caused by deficiency of the enzyme glucose-6-phosphatase.¹ Genglycos, formerly known in development as DTX401, is indicated to reduce daily cornstarch intake as an adjunct to nutritional management and is the first approved therapy for the condition.¹,² Ultragenyx announces U.S. FDA approval of Genglycos gene therapy, the first-ever FDA-approved treatment designed to treat the underlying cause of glycogen storage disease type Ia (GSDIa). News release. Ultragenyx Pharmaceutical Inc. Published August 19, 2026. Accessed August 20, 2026. RARE rises on completion of rolling submission for AAV gene therapy. "This accelerated approval reflects our confidence in the clinical evidence to date and our commitment to bringing innovative treatments to patients with rare genetic diseases while we continue to gather data to confirm long-term benefit." — Megha Kaushal, MD, MSc, acting deputy director, CBER Office of Therapeutic Products, US Food and Drug Administration · Genglycos is a one-time, AAV8-based gene therapy administered as a single intravenous infusion, designed to deliver a functional G6PC gene to liver cells to restore glucose-6-phosphatase activity and stabilize blood sugar during fasting Serious adverse reactions reported across two clinical studies included anaphylaxis, adrenal insufficiency, elevated lactate levels, and hypoglycemia, and the most common adverse reactions were increased liver transaminases, nausea, headache, constipation, and hyperglycemia.¹ Genglycos-treated patients also showed a higher rate of hypertriglyceridemia than placebo-treated patients (29% versus 8%).¹ The prescribing information carries warnings for anaphylaxis, liver toxicity, adrenal insufficiency, and tumorigenicity risk, and the therapy should not be used during pregnancy.¹ "Today's approval is a great milestone in using a gene therapy to treat this disease and improve the quality of life for people with this condition," said Karim Mikhail, B Pharm, MS, acting director of the FDA's Center for Biologics Evaluation and Research.¹
Duchenne Cell Therapy Decision Slips to November After FDA Labels New Arm Function Data a Major Amendment · Hunter Syndrome Gene Therapy Halted by FDA After Spine Scans Show Small Masses in Five Children · Gene Therapy for Glycogen Storage Disease Type Ia Wins Accelerated Approval Priced at 2.7 Million Dollars · What are inborn errors of immunity? A group of more than 500 rare genetic disorders... Duchenne Cell Therapy Decision Slips to November After FDA Labels New Arm Function Data a Major Amendment · Hunter Syndrome Gene Therapy Halted by FDA After Spine Scans Show Small Masses in Five Children · Gene Therapy for Glycogen Storage Disease Type Ia Wins Accelerated Approval Priced at 2.7 Million Dollars · What are inborn errors of immunity? A group of more than 500 rare genetic disorders, also called primary immunodeficiencies, in which a faulty gene leaves the immune system unable to work properly. Mayo Clinic joined the federal AEGIS project to build CRISPR treatments for children with inherited immune disorders. Here is what is real. Mayo Clinic has signed on as one of three clinical sites for a federally funded project that aims to do something no gene therapy program has managed yet: build a single, reusable system to treat children with rare inherited immune disorders, rather than developing an expensive therapy for each mutation one at a time. The project is called AEGIS, short for Affordable Gene Editing Therapies for Immune System Diseases of Children. It is funded by an award of up to $27.7 million from the Advanced Research Projects Agency for Health, the federal agency created to pursue high-risk medical research, and it is part of the agency's THRIVE program, which targets hereditary rare diseases with in vivo genetic medicines.
The clearance of Genglycos for a rare glycogen storage disease gives Ultragenyx a sellable voucher and momentum ahead of an eagerly anticipated study readout.
