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developmental anomaly of metabolic origin - Clinical Profile, Genes & Research | Kisho | Kisho
Rare Disease
developmental anomaly of metabolic origin
MONDO:0015327
Overview
OnsetCONGENITAL, LATE, CHILDHOOD, INFANTILE
Clinical Presentation
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.
No HPO annotations are available for this condition.
Age of onset: at birth, later in life, childhood, infancy.
GeneReviews
Clinical Guidance
Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency (HCU-CBS deficiency) is characterized by involvement of the eye, skeletal system, vascular system, and central nervous system (CNS). One to all four of the systems can be involved. Expressivity is variable for all clinical manifestations. It is not unusual for a previously asymptomatic individual to present in adulthood or earlier with only a thromboembolic event that is often cerebrovascular . Individuals with HCU-CBS deficiency can be vitamin B6 responsive, vitamin B6 nonresponsive, or partial responders to vitamin B6.
Diagnosis
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
Guidelines for the diagnosis of homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency (HCU-CBS deficiency) have been published .
Suggestive Findings
HCU-CBS deficiency should be suspected in an infant with an or a and family history. Note: (1) Individuals with untreated HCU-CBS deficiency usually develop manifestations in the first or second decade of life. (2) A symptomatic individual can have untreated HCU-CBS deficiency due to NBS not performed, false negative NBS result, or caregivers not adherent to recommended treatment after a positive NBS result.
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 developmental anomaly of metabolic origin. The disease remains an area of unmet medical need.
Gene therapy approaches for developmental anomaly of metabolic origin have been reported in the published literature.
GeneReviews
Management Guidelines
Clinical practice guidelines for management of homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency (HCU-CBS deficiency) have been published .
Evaluations Following Initial Confirmatory Diagnosis
Prognosis
Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.
GeneReviews
Surveillance Guidelines
The evaluations summarized in are recommended to monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations.
Table 10.
Homocystinuria due to Cystathionine Beta-Synthase Deficiency: Recommended Surveillance
Manifestation | Evaluation | Frequency/Comment
Metabolic/
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 developmental anomaly of metabolic origin.
190 publications have been identified in PubMed for developmental anomaly of metabolic origin. Research spans Basic Science / Preclinical (45%), Review / Meta-Analysis (20%), and Case Report / Case Series (16%).
Research Type
Count
% of Total
Laboratory research
85
45%
Data assembled from 4 of 12 sources · Last updated Oct 4, 2026, 2:18 AM 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.
NBS for HCU-CBS deficiency is primarily based on use of dried blood spots collected between 24 and 72 hours after birth to quantify methionine concentration, typically by tandem mass spect...
The clinical condition that most closely mimics homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency (HCU-CBS deficiency) is Marfan syndrome (an autosomal dominant disorder caused by pathogenic variants in FBN1), which shares the features of long, thin body habitus, arachnodactyly, and predisposition for ectopia lentis and myopia. Although ectopia lentis can also occur early in isolated sulfite oxidase deficiency (an autosomal recessive disorder caused by pathogenic variants in SUOX), this condition is clinically distinct from homocystinuria. Individuals with sulfite oxidase deficiency and Marfan syndrome have normal concentrations of plasma homocysteine and methionine.
Biomarker and diagnostic research for developmental anomaly of metabolic origin has been reported in the published literature.
To establish the extent of disease and needs in an individual diagnosed with HCU-CBS deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.
Table 4.
Homocystinuria due to Cystathionine Beta-Synthase Deficiency: Recommended Evaluations After Establishing a Diagnosis
System/Concern | Evaluation | Comment
Biochemical
| Consultation w/metabolic physician/ biochemical geneticist specialist metabolic dietitian1 | • Transfer to specialist center w/experience in mgmt of inherited metabolic diseases (strongly recommended).
Consider short hospitalization at center of expertise for inherited metabolic conditions to provide caregivers w/detailed education (re diet mgmt risk of vascular event) initiate treatment following pyridoxine challenge.
Pyridoxine (vitamin B6) challenge prior to initiation of treatment (See .)
Eyes | Ophthalmology eval | Evaluate for myopia ectopia lentis.
Orthopedic
| Clinical assessment for scoliosis, arachnodactyly, pes cavus, pectus deformity, genu valgum | Radiographs for scoliosis as needed
Neurologic
| Consultation w/neurologist | In those w/possible seizures extrapyramidal signs such as dystonia
Eval per vascular specialist | In those presenting w/vascular event
| Frequency per metabolic specialist based on severity of disorder, vitamin B6 responsiveness, adherence to treatment, age, history of venous thrombosis1
CBC iron studies (ferritin, iron, total iron-binding capacity)
Vitamin mineral testing (25-hydroxyvitamin D level, zinc)
Prealbumin
Additional labs as clinically indicated may include methylmalonic acid, serum calcium, phosphate, other vitamins trace minerals, essential fatty acids.2
| In those on methionine-restricted diet per metabolic specialist2
Ophthalmologic
| Ophthalmology exam to evaluate for myopia ectopia lentis | At least annually1
Skeletal complications
| Assess for long bone overgrowth deformity, genu valgum, pes cavus, pectus deformity, kyphosis/scoliosis, frequency of fractures. | At each visit
Radiographs for scoliosis | As needed
DXA scan | Every 3-5 yrs from adolescence; more frequent in those w/frequent fractures /or low vitamin D concentration
Cardiovascular/ Venous thromboembolism/ Stroke
| • Lipid profile to assess cardiovascular risk factors
