Huppke-Brendel syndrome in a seven months old boy with a novel 2-bp deletion in SLC33A1

Chiplunkar, Shwetha; Sankaran, Bindu Parayil; Nagappa, Madhu; Bineesh, Cheminikara; Govindaraj, Periyasamy; Gayathri, Narayanappa; Bharath, M. M. Srinivas; Arvinda, H R; Mathuranath, P. S.; Sinha, Sanjib; Taly, Arun B.

doi:10.1007/s11011-016-9854-6

Cited by 24 publications

(19 citation statements)

References 11 publications

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“…The mutation in the ATP7A gene does not necessarily lead to Menkes disease; it has also been described in patients suffering from hereditary motor neuropathy which results in the weakness of the upper limbs that progresses with age [189]. Another disease leading to the disorder of Cu metabolism is Huppke-Brendel syndrome, resulting from the mutation of the SLC33A1 gene encoding the AT-1 protein, first described in 2012 [190]. People with this syndrome have very low levels of Cu and ceruloplasmin, and often do not reach the age of 6.…”

Section: Copper (Cu)mentioning

confidence: 99%

The Role of Fe, Zn, and Cu in Pregnancy

2020

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Iron (Fe), copper (Cu), and zinc (Zn) are microelements essential for the proper functioning of living organisms. These elements participatein many processes, including cellular metabolism and antioxidant and anti-inflammatory defenses, and also influence enzyme activity, regulate gene expression, and take part in protein synthesis. Fe, Cu, and Zn have a significant impact on the health of pregnant women and in the development of the fetus, as well as on the health of the newborn. A proper concentration of these elements in the body of women during pregnancy reduces the risk of complications such as anemia, induced hypertension, low birth weight, preeclampsia, and postnatal complications. The interactions between Fe, Cu, and Zn influence their availability due to their similar physicochemical properties. This most often occurs during intestinal absorption, where metal ions compete for binding sites with transport compounds. Additionally, the relationships between these ions have a great influence on the course of reactions in the tissues, as well as on their excretion, which can be stimulated or delayed. This review aims to summarize reports on the influence of Fe, Cu, and Zn on the course of single and multiple pregnancies, and to discuss the interdependencies and mechanisms occurring between Fe, Cu, and Zn.

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Section: Copper (Cu)mentioning

confidence: 99%

The Role of Fe, Zn, and Cu in Pregnancy

2020

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“…Children with homozygous mutations in AT‐1/SLC33A1 display congenital defects, severe developmental delay, and premature death (Chiplunkar et al, 2016; Huppke et al, 2012). Patients with heterozygous mutations appear normal at birth but then develop a complicated autosomal dominant form of spastic paraplegia (Lin et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Increased transport of acetyl‐CoA into the endoplasmic reticulum causes a progeria‐like phenotype

et al. 2018

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The membrane transporter AT‐1/SLC33A1 translocates cytosolic acetyl‐CoA into the lumen of the endoplasmic reticulum (ER), participating in quality control mechanisms within the secretory pathway. Mutations and duplication events in AT‐1/SLC33A1 are highly pleiotropic and have been linked to diseases such as spastic paraplegia, developmental delay, autism spectrum disorder, intellectual disability, propensity to seizures, and dysmorphism. Despite these known associations, the biology of this key transporter is only beginning to be uncovered. Here, we show that systemic overexpression of AT‐1 in the mouse leads to a segmental form of progeria with dysmorphism and metabolic alterations. The phenotype includes delayed growth, short lifespan, alopecia, skin lesions, rectal prolapse, osteoporosis, cardiomegaly, muscle atrophy, reduced fertility, and anemia. In terms of homeostasis, the AT‐1 overexpressing mouse displays hypocholesterolemia, altered glycemia, and increased indices of systemic inflammation. Mechanistically, the phenotype is caused by a block in Atg9a‐Fam134b‐LC3β and Atg9a‐Sec62‐LC3β interactions, and defective reticulophagy, the autophagic recycling of the ER. Inhibition of ATase1/ATase2 acetyltransferase enzymes downstream of AT‐1 restores reticulophagy and rescues the phenotype of the animals. These data suggest that inappropriately elevated acetyl‐CoA flux into the ER directly induces defects in autophagy and recycling of subcellular structures and that this diversion of acetyl‐CoA from cytosol to ER is causal in the progeria phenotype. Collectively, these data establish the cytosol‐to‐ER flux of acetyl‐CoA as a novel event that dictates the pace of aging phenotypes and identify intracellular acetyl‐CoA‐dependent homeostatic mechanisms linked to metabolism and inflammation.

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“…MRI of the brain reveals cerebellar hypoplasia, hypomyelination, and wide subarachnoid spaces. To date, only a few patients have been reported as having low serum copper and ceruloplasmin levels [74,75]. It is caused by homozygous or compound heterozygous mutations in the SLC33A1 gene (OMIM 603690) located on chromosome 3q25.31.…”

Section: Huppke-brendel Syndrome (Hbs)mentioning

confidence: 99%

Genetic Disorders Associated with Metal Metabolism

Umair

Alfadhel

2019

Cells

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Genetic disorders associated with metal metabolism form a large group of disorders and mostly result from defects in the proteins/enzymes involved in nutrient metabolism and energy production. These defects can affect different metabolic pathways and cause mild to severe disorders related to metal metabolism. Some disorders have moderate to severe clinical consequences. In severe cases, these elements accumulate in different tissues and organs, particularly the brain. As they are toxic and interfere with normal biological functions, the severity of the disorder increases. However, the human body requires a very small amount of these elements, and a deficiency of or increase in these elements can cause different genetic disorders to occur. Some of the metals discussed in the present review are copper, iron, manganese, zinc, and selenium. These elements may play a key role in the pathology and physiology of the nervous system.

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Huppke-Brendel syndrome in a seven months old boy with a novel 2-bp deletion in SLC33A1

Cited by 24 publications

References 11 publications

The Role of Fe, Zn, and Cu in Pregnancy

The Role of Fe, Zn, and Cu in Pregnancy

Increased transport of acetyl‐CoA into the endoplasmic reticulum causes a progeria‐like phenotype

Genetic Disorders Associated with Metal Metabolism

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