Posts Categorized: New IEM

X-linked Cobalamin Disorder

Posted by & filed under New IEM, Part 09: ORGANIC ACIDS.

Ye et al (AJHG (2013) 93, 506-514) described a new X-linked disorder of cobalamin processing caused by transcriptional dysregulation of MMACHC (cblC, combined methylmalonic acidema and homocysteinemia). This disorder is named cblX and is caused by mutations in HCFC1. HCFC1 is a global transcriptional regulator and in addition to the biochemical phenotype, these patients also have significant neurologic consequences […]

Mutations in the nucleoside transporter gene SLC29A3 cause dysosteosclerosis, a form of osteopetrosis.

Posted by & filed under New IEM, Part 16: LYSOSOMAL DISORDERS, Part 22: CONNECTIVE TISSUE.

SLC29A3 is a lysosomal nucleoside transporter mutations in which cause histiocytosis–lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. We have now identified mutations in this gene in dysosteosclerosis, a form of osteopetrosis characterized by the additional features of platyspondyly, remarkable acquired metaphyseal osteosclerosis and red-violet macular atrophy of skin. We […]

Inborn error of tRNA formylation

Posted by & filed under New IEM.

Tucker EJ, et al. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab. 2011 Sep 7;14(3):428-34 Next-generation sequencing of nuclear-encoded mitocondrial proteins in two unrelated patients with Leigh syndrome and combined OXPHOS deficiency revealed a new inborn error of formylation. This study by the groups of David Thorburn and […]

Glycerol-3-Phosphate Dehydrogenase deficiency

Posted by & filed under Exome sequencing, New IEM.

Basel-Vanagaite L. et al. Transient Infantile Hypertriglyceridemia, Fatty Liver, and Hepatic Fibrosis Caused by Mutated GPD1, Encoding Glycerol-3-Phosphate Dehydrogenase 1. Am J Hum Genet. 2012 Jan 4 In several individuals with childhood hypertriglyceridemia followed by liver fibrosis, this group identified mutations in GDP1, encoding Glycerol-3-Phosphate Dehydrogenase 1. The enzyme GPD1 reversibly converts glycerol-3-phosphate (G3P) in […]

Adenosine Kinase Deficiency

Posted by & filed under Exome sequencing, New IEM.

Two siblings with developmental delay, liver dysfunction and hypermethioninemia were investigated by exome sequencing. A homozygous missense mutation was identified in adenosine kinase, which could explain the block in the methionine cycle. Additional families were identified, and the mutations affected enzymatic function. The mouse deficient in adenosine kinase, described previously, displays phenotypic similarities, and to […]

Defective phosphatidylcholine biosynthesis and muscular dystrophy

Posted by & filed under New IEM, _.

Several individuals with congenital muscular dystrophy were recently described to have mutations in the gene encoding for choline kinase beta, inherited in an autosomal recessive manner. This is the first enzymatic step in a de novo biosynthetic pathway for phosphatidylcholine. Pathological features include intellectual disability, muscle wasting, and enlarged mitochondria on muscle biopsy. A mouse […]

New Channelopathies

Posted by & filed under New IEM.

Three metabolic disorders caused by channel mutations have been described: a renal Fanconi syndrome with mutations in NaPi-IIa causing impaired renal phosphate reabsorption (Magen et al., 2010, N Engl J Med 362:1102-09). ATP7A, encoding a copper transporter causing Menkes disease and occipital horn syndrome, can also be the cause of X-Linked Distal Hereditary Motor Neuropathy […]


Posted by & filed under New IEM.

There are over 40 known congenital disorders of glycosylation (CDGs), and a reformulation of their nomenclature has been proposed by Dr. Jaak Jaeken, who described the first CDG (Jaeken et al, 2009, Biochim Biophys Acta 1792:825-6). A new CDG has now been identified in several families (Cantagrel et al, 2010, Cell 142:203-17). Patients present notably […]

Inborn error of endocannabinoid metabolism

Posted by & filed under New IEM.

An inborn error of endocannabinoid metabolism has been described in 19 patients (Fiskerstrand et al. 2010, Am J Hum Genet 87:410-7), clinically characterized by polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts (PHARC). ABHD12 as an integral membrane protein with an active site located on the extracellular side. The mutated enzyme normally hydrolyzes 2-arachidonoyl glycerol, […]


Posted by & filed under New IEM.

The conserved oligomeric Golgi (COG) complex is located in the cytosol and aids in the sorting and glycosylation of Golgi-resident enzymes and secreted proteins. A new congenital disorder of glycosylation has been described involving this complex: CDG-IIL caused by COG6 mutations (Lübbehusen et al., 2010, Hum Mol Genet 19:3623-33). Clinical presentation is a severe neurologic […]