Inherited and other metabolic disorders

Lathosterolosis

Lathosterolosis (sterol C5-desaturase deficiency, SC5D deficiency) is an ultra-rare autosomal recessive cholesterol biosynthesis disorder from SC5D mutations, causing dysmorphism, limb anomalies, cataracts, developmental delay, and liver disease.

LCAT deficiency

LCAT deficiency (lecithin-cholesterol acyltransferase deficiency), including familial LCAT deficiency (FLD) and fish-eye disease (FED), is a rare autosomal recessive lipoprotein disorder causing corneal opacities, hemolytic anemia, very low HDL-C, and progressive renal failure.

Lesch–Nyhan syndrome

Lesch–Nyhan syndrome, an X-linked HPRT1 disorder (HPRT deficiency, Lesch–Nyhan disease), causes hyperuricemia, dystonia, and compulsive self-injury; allopurinol controls uric acid only.

LIPE-related familial partial lipodystrophy

LIPE-related familial partial lipodystrophy (FPLD6, OMIM 615980) is a rare autosomal recessive lipodystrophy caused by LIPE mutations encoding hormone-sensitive lipase, causing distal lipoatrophy, visceral fat gain, myopathy, and vitiligo.

Lipodystrophy

Lipodystrophy: rare disorders of selective body-fat loss, genetic (CGL, FPLD; AGPAT2, BSCL2, LMNA genes) or acquired (AGL, APL, HIV-related), causing insulin resistance, diabetes, hypertriglyceridemia; treated with diet, metreleptin, statins.

Lysinuric protein intolerance

Lysinuric protein intolerance (LPI, hyperdibasic aminoaciduria, OMIM 222700) is an autosomal recessive SLC7A7 transporter defect causing lysine, arginine, and ornithine loss, urea cycle dysfunction, and lung, kidney, and immune complications.

Lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency (LAL-D), formerly split into Wolman disease and cholesteryl ester storage disease, is an autosomal recessive LIPA-gene disorder causing lipid buildup, liver disease, and dyslipidemia, treated with sebelipase alfa.

Malonic aciduria

Malonic aciduria, also called malonyl-CoA decarboxylase or MLYCD deficiency, is an autosomal recessive organic acidemia from MLYCD gene mutations on 16q24, causing developmental delay, hypotonia, hypoglycemia, and cardiomyopathy, diagnosed by elevated urinary malonic acid and blood malonylcarnitine.

Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome

MDPL syndrome (MDP syndrome, OMIM 615381) is an ultra-rare autosomal dominant progeroid lipodystrophy caused by heterozygous POLD1 mutations, most often the recurrent de novo p.Ser605del deletion, causing mandibular hypoplasia, sensorineural deafness, lipodystrophy, and insulin resistance, distinguished from Werner syndrome by absent cataracts.

Maternal phenylketonuria syndrome

Maternal phenylketonuria syndrome (maternal PKU syndrome, MPKUS) is a pattern of birth defects in babies of pregnant women with PKU, caused by high phenylalanine crossing the placenta.

Metabolic acidosis

Metabolic acidosis: primary fall in blood bicarbonate with compensatory low PCO2, classified as high anion gap (ketoacidosis, lactic acidosis, renal failure, toxins) or normal gap (bicarbonate loss); diagnosed by ABG and electrolytes, treated by cause.

Methionine adenosyltransferase I/III deficiency

Methionine adenosyltransferase I/III deficiency, also called Mudd's disease, is a rare inherited metabolic disorder in which MAT1A gene mutations raise blood methionine; most people are unaffected, but some develop neurological problems including brain demyelination.

Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

MCEE deficiency (OMIM 251120, ORPHA 308425), an ultra-rare autosomal recessive inborn error of metabolism causing mild-to-moderate persistent methylmalonic acid elevation, B12-nonresponsive, with a clinical spectrum from asymptomatic to acute decompensation.

Methylmalonic acidemia with homocystinuria

Methylmalonic acidemia with homocystinuria, also called cobalamin C (cblC) disease, is an inherited vitamin B12 metabolism defect causing methylmalonic acid and homocysteine buildup; genes include MMACHC, MMADHC, LMBRD1, ABCD4, HCFC1.

Microcephaly-congenital cataract-psoriasiform dermatitis syndrome

Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, also known as SMO deficiency, is a rare autosomal recessive disorder of cholesterol metabolism caused by mutations in the MSMO1 gene.

Microvillus inclusion disease

Microvillus inclusion disease (MVID, Davidson disease, congenital microvillus atrophy) is a rare autosomal recessive congenital enteropathy causing life-threatening neonatal secretory diarrhea, caused mainly by MYO5B mutations and treated with lifelong parenteral nutrition.

Mild hyperphenylalaninemia

Mild hyperphenylalaninemia (mild HPA), also known as non-PKU hyperphenylalaninemia or MHP, is the mildest form of phenylalanine hydroxylase deficiency, an inherited metabolic disorder with blood phenylalanine of 120 to 600 micromol/L.

Mitochondrial pyruvate carrier deficiency

Mitochondrial pyruvate carrier deficiency (MPYCD, OMIM 614741) is a rare autosomal recessive MPC1-related disorder causing neonatal lactic acidosis, elevated pyruvate with normal lactate/pyruvate ratio, encephalopathy, and developmental delay.

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D, Crotonase deficiency): rare autosomal recessive ECHS1 disorder of valine catabolism causing neonatal or infantile encephalopathy, dystonia, basal ganglia lesions, and lactic acidosis; neonatal onset predicts mortality.

Morquio syndrome

Morquio syndrome (mucopolysaccharidosis type IV, Morquio-Brailsford disease) is an autosomal recessive lysosomal storage disorder affecting the skeleton; type A stems from GALNS deficiency, type B from GLB1, treated with elosulfase alfa ERT.

Mucolipidosis type II

Mucolipidosis type II, or I-cell disease (MLII alpha/beta), a severe autosomal recessive lysosomal storage disorder from GNPTAB mutations causing mannose-6-phosphate tagging failure, presenting at birth with dysostosis multiplex, cardiac and respiratory disease, and death in early childhood.

Mucolipidosis type III

Mucolipidosis type III (pseudo-Hurler polydystrophy), MLIII alpha/beta (GNPTAB) or gamma (GNPTG), is a rare autosomal recessive lysosomal storage disorder from partial GlcNAc-1-phosphotransferase deficiency, causing progressive joint stiffness, short stature, and dysostosis multiplex with median survival of 62 years.

Mucolipidosis type IV

Mucolipidosis type IV (MLIV, OMIM 252650) is an ultra-rare autosomal recessive lysosomal storage disorder caused by MCOLN1 mutations, marked by psychomotor delay, progressive vision loss, achlorhydria, and a 2026 FDA-authorized gene therapy trial.

Mucopolysaccharidosis

Mucopolysaccharidosis (MPS), also called mucopolysaccharidoses, is a group of rare inherited lysosomal storage diseases in which enzyme deficiency causes glycosaminoglycan buildup; types include Hurler, Hunter, Sanfilippo, and Morquio syndromes, treated with ERT, HSCT, and gene therapy.

Mucopolysaccharidosis type 1

Mucopolysaccharidosis type 1 (MPS I, Hurler syndrome, alpha-L-iduronidase deficiency) is a rare autosomal recessive lysosomal storage disorder causing dermatan and heparan sulfate accumulation, treated with HSCT and laronidase enzyme replacement therapy.

Mucopolysaccharidosis type 10

Mucopolysaccharidosis type 10 (MPS10, MPS type X, ARSK deficiency) is an autosomal recessive lysosomal storage disorder from biallelic ARSK variants on 5q15, causing childhood short-trunk short stature with skeletal, cardiac, and ophthalmologic findings but normal cognition.

Mucopolysaccharidosis type 6

Mucopolysaccharidosis type 6 (MPS VI, Maroteaux-Lamy syndrome) is a rare autosomal recessive lysosomal storage disease caused by arylsulfatase B (ARSB) deficiency, treated with galsulfase enzyme replacement therapy since 2005.

Mucopolysaccharidosis type 7

Mucopolysaccharidosis type 7 (MPS VII, Sly syndrome, beta-glucuronidase deficiency) is an ultra-rare autosomal recessive lysosomal storage disease caused by GUSB mutations, treated with vestronidase alfa enzyme replacement therapy.

Multiple mitochondrial dysfunctions syndrome type 1

MMDS1, or NFU1 deficiency (MIM 605711), is an ultra-rare autosomal recessive mitochondrial disease from NFU1 gene defects on 2p13.3, causing infantile encephalopathy, lactic acidosis, hyperglycinemia, and pulmonary arterial hypertension, typically fatal in early infancy.