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An inherited metabolic disease that is has its basis in the disruption of carbohydrate metabolic process.
No HPO annotations are available for this condition.
NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) is a multisystemic neurodevelopmental disorder in which individuals most commonly exhibit a tetrad of developmental delay / intellectual disability, hyperkinetic movement disorder, hypolacrima, and elevated transaminases during early childhood [, , , , ]. Diagnosis has been achieved at ages ranging from three months to 20 years, mostly through broad molecular testing, such as exome analysis. While most individuals with NGLY1-CDDG survive into early adulthood, with a relatively stable clinical course , death during infancy from unclear causes has been reported.
Formal diagnostic criteria have not been established.
NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) should be suspected in individuals with the following clinical features and supportive laboratory findings. Clinical features include:
Developmental delay / intellectual disability, most often in the severe to profound range
No approved treatments are currently available for inborn carbohydrate metabolic disorder. The disease remains an area of unmet medical need.
Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG), the evaluations summarized (if not performed as part of the initial evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis of NGLY1-CDDG
In the absence of formal surveillance guidelines, the authors recommend the following:
Annual follow up by:
Pediatrician or internist
Physical medicine and rehabilitation medicine
1 clinical trial registered. Pipeline includes 1 NA.
269 publications have been identified in PubMed for inborn carbohydrate metabolic disorder. Kisho has analyzed 182 by research type. Research spans Case Report / Case Series (27%), Basic Science / Preclinical (25%), and Review / Meta-Analysis (21%).
Research Type | Count | % of Total |
|---|---|---|
Patient case studies | 49 | 27% |
Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 8:41 AM UTC
European rare disease database
Genetic and Rare Diseases Info Center
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
Hypo- or alacrima
Supportive laboratory findings include elevated ALT and AST during early childhood that spontaneously normalize. Note: Typical serum screening tests for congenital disorders of glycosylation (i.e., analysis of serum transferrin glycoforms, N and O glycan profiling) will NOT reliably detect NGLY1-CDDG (see , Biochemical).
The diagnosis of NGLY1-CDDG is established...
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
The tetrad of developmental delay / cognitive impairment, hyperkinetic movement disorder, hypo/alacrima, and elevated transaminases during early childhood is pathognomonic of NGLY1-CDDG [, , , , ]. However, other multisystemic disorders and conditions that feature variable neurologic phenotypes, including seizures, chorea, athetosis, dystonia, myoclonus, tremors, ataxia, and dysmetria, are in the differential diagnosis.
Table 2.
Disorders to Consider in the Differential Diagnosis of NGLY1-Related Congenital Disorder of Deglycosylation
Disorder | Gene(s) | MOI | Clinical Features
Overlapping | Distinguishing
Congenital disorders of glycosylation (CDGs) (see Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview.) | See footnote 1. | ARXL | • Intrauterine growth restriction
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
Inborn carbohydrate metabolic disorder is included in newborn screening programs (Tyrosinemia Type I) in all 50 states and 3 territories.
Biomarker and diagnostic research for inborn carbohydrate metabolic disorder has been reported in the published literature.
System/Concern | Evaluation | Comment |
|---|---|---|
Eyes | Ophthalmologic eval for hypolacrima retinal disease | — |
ENT/Mouth | Auditory brain stem evoked potentials | — |
Respiratory | Sleep study | If review of systems reveals snoring or symptoms concerning for sleep apnea |
Gastrointestinal | Nutrition eval to optimize intake | Feeding swallowing eval if indicated; Transaminase levels; Eval for constipation |
Musculoskeletal | Radiologic orthopedic assessment incl DXA scan | To evaluate bone health help manage scoliosis, coxa valga, /or contractures |
Skin | QSWEAT analysis to evaluate for hypohydrosis | Neurologic |
Endocrinologic | Vitamin D level | To assess for vitamin D deficiency Hematologic/ |
Lymphatic | Protein C; factor II, IX, XI; fibrinogen levels | Consultation w/hematologist if abnormal Miscellaneous/ |
Other | Speech language eval | Referral to speech therapist if indicated Rehabilitation team eval |
Treatment of Manifestations in Individuals with NGLY1-CDDG Manifestation/Concern | Treatment | Considerations/Other |
Hypolacrima | Lubricating eye drops /or bland ointments | — |
Hearing loss | Standard treatment | See Hereditary Hearing Loss and Deafness Overview. |
Sleep apnea | Routine management | — |
Oromotor deficits leading to feeding problems | Feeding therapy; supplemental tube feeding if indicated | Referral to gastroenterologist |
Constipation | Standard management | Referral to gastroenterologist if refractory to typical medical management |
Abnormal hematologic /or gastroenterologic labs | Follow up w/hematologist gastroenterologist | — |
Scoliosis osteopenia | Routine management | — |
Hypohydrosis | Adequate access to water cool environment (AC, wet T-shirt, /or spray bottle of water) | Cooling vests may be helpful in hot climates. |
Seizures | Standard treatment | Referral to neurologist for those w/refractory or severe seizures |
Vitamin D deficiency | Supplemental vitamin D | — |
Any condition requiring surgical intervention | Surgery best performed in centers w/surgeons anesthesiologists experienced in care of those w/metabolic disorders special needs | AC = air conditioning The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. |
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
Hot environment should be avoided by those with hypohydrosis.
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
No FDA-approved treatments for NGLY1-CDDG exist. Enzyme replacement therapy is currently being evaluated in the pre-clinical arena. Pre-clinical screens for endo-beta-N-acetylglucosaminidase (ENGase) inhibitors are underway . Large-scale compound screens on model organisms and cell lines are being evaluated. 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.
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
1 trial found
Neurology
Nutrition
Follow up as recommended by:
Developmental pediatrician
Gastroenterologist/hepatologist
Audiologist
Clinical or biochemical geneticist
Source: GeneReviews — "NGLY1-Related Congenital Disorder of Deglycosylation"
Laboratory research
45 |
25% |
Research summaries | 38 | 21% |
Disease patterns and progression | 16 | 9% |
Testing and diagnosis research | 13 | 7% |
Clinical study results | 12 | 7% |
New treatment approaches | 8 | 4% |
Other research | 1 | 1% |
Suarez DA (2026). [PMID: 41880697](https://pubmed.ncbi.nlm.nih.gov/41880697/). *Mol Genet Metab*. [Review / Meta-Analysis]
Rodrigues A (2026). [PMID: 41564618](https://pubmed.ncbi.nlm.nih.gov/41564618/). *Mol Genet Metab*. [Clinical Trial Publication]
Köprülü Ö (2026). [PMID: 41399023](https://pubmed.ncbi.nlm.nih.gov/41399023/). *J Pediatr Endocrinol Metab*. [Case Report / Case Series]
Betesh-Abay B (2026). [PMID: 41898592](https://pubmed.ncbi.nlm.nih.gov/41898592/). *Int J Mol Sci*. [Review / Meta-Analysis]
Burke E (2026). [PMID: 41539482](https://pubmed.ncbi.nlm.nih.gov/41539482/). *Pediatrics*. [Case Report / Case Series]
Morana E (2026). [PMID: 41611076](https://pubmed.ncbi.nlm.nih.gov/41611076/). *Eur J Med Genet*. [Case Report / Case Series]
Stone WL (2026). [PMID: 28846219](https://pubmed.ncbi.nlm.nih.gov/28846219/). *Unknown Journal*. [Review / Meta-Analysis]
Tokic S (2026). [PMID: 38776074](https://pubmed.ncbi.nlm.nih.gov/38776074/). *J Physiol*. [Basic Science / Preclinical]
Murdoch M (2026). [PMID: 41881488](https://pubmed.ncbi.nlm.nih.gov/41881488/). *BMJ Case Rep*. [Case Report / Case Series]
Grünert SC (2026). [PMID: 41554131](https://pubmed.ncbi.nlm.nih.gov/41554131/). *J Inherit Metab Dis*. [Epidemiology / Natural History]
AI-curated news mentioning inborn carbohydrate metabolic disorder
Updated Jul 31, 2026
Four IPOs are currently scheduled for the week ahead, featuring three biotechs and a California bank. Four IPOs are currently scheduled for the week ahead, featuring three biotechs and a California bank. - Renaissance Capital Four IPOs are currently scheduled for the week ahead, featuring three biotechs and a California bank. Mega-issuer SpaceX (SPCX) will also be in focus as it reports earnings for the first time as a public company ahead of a partial lock-up release that will more than double the tradable float. Cardiovascular disease biotech Braveheart Bio (BRVE) is set to raise $300 million at a $1.4 billion market cap. Immune system-focused biotech Attovia Therapeutics (ATTO) plans to raise $200 million at a $649 million market cap. Attovia is developing biologic therapies for immune-mediated diseases using its ATTOBODY platform to create next-generation antibody therapeutics targeting validated immune pathways. Its commercial real estate lending franchise accounted for roughly 90% of its loan portfolio as of June 30, 2026. River City has also developed a niche serving California Community Choice Aggregator entities, although the resulting deposit base is fairly concentrated. Metabolic disorder biotech Vogenx (VOGX) plans to raise $75 million at a $173 million market cap.
RANCHO CORDOVA, Calif., May 07, 2026 (GLOBE NEWSWIRE) -- SK pharmteco today announced a strategic partnership with Axle Informatics and the National Institutes of Health (NIH) to advance the development of gene therapies for rare diseases. The inaugural program under this partnership focuses on producing lentiviral vectors (LVV) to treat rare inherited blood and metabolic disorders. SK pharmteco has worked closely with NIH investigators to advance this effort. As part of that work, SK pharmteco manufactured drug substance intended for future ex vivo transduction of patients’ CD34+ hematopoietic stem cells and managed batch-release testing, with most analytical assays performed in-house at its specialized laboratories. “Axle is focused on connecting capabilities across the NIH environment, and our collaboration with SK pharmteco adds essential manufacturing strength to help NIH advance promising gene therapies for patients in need.” · This partnership highlights SK pharmteco’s ability to serve as a strong technical partner for both emerging biotech firms and large-scale public institutions. It also reflects SK pharmteco’s broader efforts to support rare disease innovators through partnership models designed to help advance complex programs into the clinic. "Collaborating with the NIH and Axle Informatics marks an important step in our efforts to support patients with rare diseases,” said John Lee, Global Head of Viral Vector at SK pharmteco. “Rare disease programs often operate under significant development and funding constraints, making reliable technical execution and flexible partnerships especially important. Get daily news updates when you subscribe to GenePool!
The FDA announces a new framework to expedite treatment approvals for rare genetic diseases, allowing for a single clinical trial to cover multiple mutations of the same gene. This initiative aims to enhance access to therapies for children with rare diseases, exemplified by the successful treatment of KJ Muldoon with a customized gene-editing therapy.