Rare disorder reference

Severe joint hypermobility with congenital bilateral hip dislocation. Type I collagen exon-6 skipping.

Reclassified into the EDS family in 2017. Extreme corneal thinning with ocular fragility.

Severe progressive cardiac valve disease in the EDS spectrum. COL1A2 biallelic null variants.

The original Ehlers-Danlos. Hyperextensible skin, atrophic scarring, joint hypermobility. Type V collagen.

Looks like classical EDS but with TNXB tenascin-X deficiency. Atrophic scars are absent.

Identified in 2018. AEBP1-associated, with overlapping features of classical and arthrochalasia EDS.

Profoundly fragile, sagging skin from ADAMTS2 deficiency. Severe craniofacial features.

Symptomatic generalized hypermobility that does not meet hEDS criterion 2. Real diagnosis, similar management.

The most common EDS subtype. Diagnosis is clinical: the 2017 criteria, no confirmatory gene.

Congenital kyphoscoliosis with severe muscle hypotonia. PLOD1 lysyl hydroxylase or FKBP14 deficiency.

Congenital multiple contractures with characteristic craniofacial features. CHST14 or DSE deficiency.

Congenital muscle hypotonia and atrophy with proximal joint contractures. COL12A1 defects.

Severe early-onset periodontitis with skin and joint findings. Complement protein C1r or C1s defects.

Short stature with progressive spinal deformity. Three known molecular forms.

The dangerous form. Type III collagen defects cause arterial and visceral fragility.

A leucine-catabolism disorder that can mimic Reye syndrome. Sudden metabolic crisis between healthy intervals.

Frequently detected, often asymptomatic. The panel's overdiagnosis debate plays out here.

Urea cycle disorder. Hyperammonemia is the danger. Ammonia scavengers and protein restriction are the levers.

Episodic ketoacidosis triggered by illness or fasting. The emergency protocol problem in one disease.

Treated with oral biotin. Untreated, it causes neurologic damage. One of the cleanest screening wins.

Carnitine transport failure. Treated with oral carnitine. Sudden cardiac death is the prevented outcome.

Urea cycle disorder. Severe neonatal hyperammonemia in classic form; milder late-onset forms exist.

GALT enzyme deficiency. Lactose-free formula prevents acute neonatal liver failure. Long-term outcomes are mixed.

The condition that started newborn screening. Phenylalanine restriction prevents severe intellectual disability.

21-hydroxylase deficiency. Salt-wasting crisis is the screening target. Glucocorticoid replacement is lifelong.

Pulse oximetry screening for ductal-dependent lesions. Saves lives by catching defects before discharge.

CFTR defect. Modulator therapies (Trikafta) transformed life expectancy. Screening enables early nutrition support.

X-linked progressive muscle-wasting disease. Newest addition to the panel as screening enables early intervention.

Lysosomal storage disorder. Atidarsagene autotemcel gene therapy approved 2024. Recently added to RUSP.

Encephalopathic crisis preventable by screening. One of the most dramatic before-and-after stories on the panel.

Cerebral creatine deficiency. Treatable with creatine and ornithine supplementation if caught before symptoms.

Universal newborn hearing screening. Early identification enables language development support.

Compound heterozygosity for HbS and HbC. Milder than HbSS but with retinopathy and avascular necrosis risk.

Multiple carboxylase deficiency that responds to biotin. A treatable mimic of catastrophic illness.

Methionine metabolism defect. B6-responsive and non-responsive forms. Lens dislocation and thrombosis are hallmarks.

X-linked lysosomal storage disorder. Enzyme replacement therapy and now gene therapy in trials.

Lysosomal storage disorder. Pre-symptomatic stem cell transplant alters the trajectory of severe forms.

Sweaty-feet odor, episodic crisis. Treatment with glycine and carnitine works when started early.

Long-chain fatty acid oxidation defect. Maternal HELLP risk during pregnancy is a distinctive feature.

Branched-chain amino acid disorder. Urine smell gives the name. Liver transplant cures the metabolic disease.

The most common fatty acid oxidation disorder. Sudden death during fasting illness is the prevented outcome.

Vitamin B12 metabolism defects. Some forms respond dramatically to high-dose hydroxocobalamin.

Severe organic acidemia. Crisis presentation common. Liver and kidney transplants increasingly offered.

Hurler, Hurler-Scheie, and Scheie phenotypes. Stem cell transplant for severe forms; ERT for milder.

Glycogen storage disease type II. Enzyme replacement therapy works best when started before symptoms.

The most common condition detected by newborn screening. Levothyroxine fully prevents intellectual disability.

Severe neonatal-onset organic acidemia. Cardiomyopathy is a major late complication.

Compound heterozygosity for sickle cell and beta-thalassemia. Phenotype ranges from severe to mild.

Bubble-baby disease. Pre-symptomatic stem cell transplant is curative. The clearest screening case study.

Homozygous HbS. The most common severe hemoglobinopathy. Hydroxyurea, transfusion, and now gene therapy.

SMN1 deletion. Three approved disease-modifying therapies. Pre-symptomatic treatment changes the disease.

Severe fatty acid oxidation defect. Cardiomyopathy and rhabdomyolysis are major complications.

Tyrosine metabolism defect. Liver failure and hepatocellular carcinoma risk. Nitisinone (NTBC) transformed outcomes.

Long-chain fatty acid oxidation defect. Severity ranges from neonatal cardiac to adult-onset rhabdomyolysis.

The Lorenzo's Oil disease. Boys identified before symptoms can receive monitoring and pre-symptomatic transplant.

The MFSD8 form of Batten disease. Mila Makovec's case produced milasen, the first patient-customized antisense oligonucleotide therapy.

ALS caused by FUS gene mutations. Jaci Hermstad's case produced jacifusen, the ASO Ionis is now advancing toward Phase 3 after a 12-patient case series in the Lancet 2025.

Heterotrimeric G-protein Go alpha-subunit mutations. The Bow Foundation funds the Friedman / n-Lorem allele-selective ASO program for gain-of-function GNAO1 variants.

USP7 haploinsufficiency. Tess Bigelow was the eighth person diagnosed worldwide; her father Bo Bigelow's Reddit post led to the case identification by Mike Fountain at Baylor in 2014.

KIF1A motor protein mutations. Susannah Rosen was the first patient treated; n-Lorem developed her allele-selective ASO, with Wendy Chung's KAND Natural History Study as the trial-ready dataset.

GABA transporter (GAT-1) loss-of-function. Amber Freed's son Maxwell was the first identified case for the SLC6A1 Connect / Steven Gray AAV9 gene therapy program.

AP4M1 deficiency. Michael Pirovolakis was the first patient dosed in 2022; his father Terry now runs Elpida Therapeutics, the n-of-few gene therapy company built on the SPG50 trial.